Cutting Edge: Alum Adjuvant Stimulates Inflammatory Dendritic Cells through Activation of the NALP3 Inflammasome

TLDR

Adjuvants are vaccine additives that stimulate the immune system without possessing specific antigenic activity. The study proposes that NALP3 inflammasome agonists should be considered as vaccine adjuvants alongside TLR stimulators. Adaptive immunity to OVA‑alum is initiated by monocytic dendritic cell precursors that expand antigen‑specific T cells in a NALP3‑dependent manner. Alum triggers IL‑1β release from macrophages and dendritic cells, a process abrogated in cells lacking NALP3 inflammasome components, and NALP3 is required for innate responses to OVA‑alum, with its deficiency markedly reducing early IL‑1β production and inflammatory cell influx in vivo.

Abstract

Adjuvants are vaccine additives that stimulate the immune system without having any specific antigenic effect of itself. In this study we show that alum adjuvant induces the release of IL-1beta from macrophages and dendritic cells and that this is abrogated in cells lacking various NALP3 inflammasome components. The NALP3 inflammasome is also required in vivo for the innate immune response to OVA in alum. The early production of IL-1beta and the influx of inflammatory cells into the peritoneal cavity is strongly reduced in NALP3-deficient mice. The activation of adaptive cellular immunity to OVA-alum is initiated by monocytic dendritic cell precursors that induce the expansion of Ag-specific T cells in a NALP3-dependent way. We propose that, in addition to TLR stimulators, agonists of the NALP3 inflammasome should also be considered as vaccine adjuvants.